title: Risk prediction for malignant conversion of oral epithelial dysplasia by hypoxia related protein expression.
abstract: Increased aerobic glycolysis is a unique finding in cancers and hypoxia-related proteins are associated with aerobic glycolysis. Therefore, we aimed to investigate whether hypoxia-related proteins can be predictive markers for malignant conversion of oral premalignant lesions with epithelial dysplasia (OED).
  
  
  
  Expression of HIF-1α, Glut-1 and CA9 were detected in clinical samples of eight normal oral mucosa, 85 transitional areas of oral squamous cell carcinoma (OSCC) and 28 OED with or without malignant conversion using immunohistochemistry and were also comparatively detected in immortalised human oral keratinocyte (IHOK) and OSCC cell lines under hypoxia using immunoblotting.
  
  
  
  Sequential expression of HIF-1α, Glut-1 and CA9 was found both in transitional areas of OSCC and cell lines of IHOK and OSCC under hypoxia, supporting hypoxia-aerobic glycolysis-acidosis axis. Expression of all proteins showed significant association with malignant conversion of OED and CA9 was an independent risk factor of malignant transformation of OED. But the predictability of malignant transformation was improved when all three proteins were applied together.
  
  
  
  High expression of CA9 was an independent predictive marker of malignant conversion. Moreover, the combined application of these three proteins may be useful to assess the risk of malignant conversion of OED.
authors.affiliation: Oral Cancer Research Institute, College of Dentistry, Yonsei University, Seoul, Republic of Korea.
authors.forename: Xianglan
authors.initials: X
authors.lastname: Zhang
authors.forename: Seonhui
authors.initials: S
authors.lastname: Han
authors.forename: Hye-Yeon
authors.initials: HY
authors.lastname: Han
authors.forename: Mi Heon
authors.initials: MH
authors.lastname: Ryu
authors.forename: Ki-Yeol
authors.initials: KY
authors.lastname: Kim
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Choi
authors.forename: In-Ho
authors.initials: IH
authors.lastname: Cha
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009055:Mouth / Q000378:metabolism / Q000473:pathology*; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D011230:Precancerous Conditions / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D011237:Predictive Value of Tests; D012307:Risk Factors
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D051272:Glucose Transporter Type 1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C495677:SLC2A1 protein, human; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases